Synthesis of Carborane-Containing Flavone and Flavonol Analogues as ER Agonists and COX Inhibitors

Flavones
and flavonols are natural products and privileged structures
with diverse bioactivities. Carboranes are considered a three-dimensional
bioisosteric surrogate for phenyl rings. Herein, the terminal phenyl
group of flavones and flavonols was replaced with carborane, and a
series of carborane-containing flavone and flavonol analogues were
successfully prepared. These compounds exhibited estrogen receptor
(ER) agonist activities. Compound 1 showed an EC50 of 0.87 ± 0.07 μM for ERα and a selectivity
of 12.8-fold toward ERβ. These compounds also showed moderate
inhibitory activities toward COX-1 and COX-2.